Neoadjuvant PD-1 Blockade Combined With Chemotherapy Followed by Concurrent Immunoradiotherapy for Locally Advanced Anal Canal Squamous Carcinoma Patients

Anal Cancer Clinical Trial

Official title:

Neoadjuvant PD-1 Blockade Combined With Chemotherapy Followed by Concurrent Immunoradiotherapy for Locally Advanced Anal Canal Squamous Carcinoma Patients

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05060471
• Other study ID #: B2021-137-01
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: September 8, 2021
• Est. completion date: December 30, 2023

Study information

• Verified date: April 2023
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Locally Advanced Anal Canal Squamous Carcinoma Patients will be enrolled and given four cycles of neoadjuvant PD-1 antibody toripalimab combined with docetaxol and cisplatin, followed by radiotherapy and two cycles of concurrent toripalimab. Treatment outcomes and toxicities will be evaluated.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 27
• Est. completion date: December 30, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

(1) Histology confirmed as anal canal squamous carcinoma;

1. Clinical stage I-III

2. No distant metastasis;

3. Age: 18-75 years old;

4. ECOG 0-1 score

5. Adequate bone marrow, liver, kidney function

6. if HIV infected, HIV loading is below the lower limit (<20 copy </ ml), with the number of CD4+T cells > 300> ml

7. Non-pregnant or lactating women;

8. No other malignant disease within 5 years before diagnosis of anal cancer squamous carcinoma (except endocervical cancer in situ or skin basal cell carcinoma which had been cured); no other malignant disease beside anal cancer squamous carcinoma

9. No other serious disease leading to shortened survival.

10. No previous anal canal surgery or anal tumor resection (except for biopsy);

11. No chemotherapy received within the previous 5 years;

12. No previous pelvic radiation;

13. No biological treatment received in the previous 5 years;

14. No previous immunotherapy received.

Exclusion Criteria:

1. Diagnosed as stage I and well differentiated squamous cell carcinoma

2. Distant metastasis

3. Received radiation therapy in abdominal or pelvic regions

4. Pregnant, lactating woman patient or fertile but lacks adequate contraceptives

5. Infectious disease: Active phase chronic hepatitis B or hepatitis C (high copies of virus DNA); Other serious active clinical infection

6. Patients with active tuberculosis (TB) are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening;

7. Chronic inflammatory colorectal disease, unrelieved ileus

8. Dyscrasia or organ decompensation

9. Allergic to research-related drugs

10. Severe hypertension with poor drug control;

11. Epilepsy require medical treatment (such as steroid or antiepileptic therapy);

12. Drug abuse and medical, psychological or social factors that may interfere with patients' participation in the study or affect the evaluation of the study;

13. Patients have any active autoimmune diseases or a history of autoimmune diseases (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism and decreased thyroid function; patients with vitiligo or with complete remission of asthma in childhood and without any intervention in adulthood may be included; patients with asthma requiring bronchodilators intervention are not included.

14. Received any anti-infection vaccine (e.g. influenza vaccine, chickenpox vaccine, etc.) within 4 weeks before enrollment;

15. Complications require long-term treatment with immunosuppressive drugs, or requiring systemic or local use of immunosuppressive corticosteroids(>10mg/day prednisone or other therapeutic hormones);

16. Any unstable condition or which endangers the patients' safety and compliance;

17. Refuses to sign informed consent

Related Conditions & MeSH terms

• Anal Canal Cancer
• Anal Cancer
• Anal Squamous Cell Carcinoma
• Anus Neoplasms
• Carcinoma
• Carcinoma, Squamous Cell

Intervention

Drug:
• Toripalimab
Four cycles of neoadjuvant PD-1 antibody toripalimab combined with docetaxol and cisplatin, followed by radiotherapy and two cycles of concurrent toripalimab.

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (24)

Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB 3rd, Thomas CR Jr, Mayer RJ, Haddock MG, Rich TA, Willett C. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized cont — View Citation

Amirian ES, Fickey PA Jr, Scheurer ME, Chiao EY. Anal cancer incidence and survival: comparing the greater San-Francisco bay area to other SEER cancer registries. PLoS One. 2013;8(3):e58919. doi: 10.1371/journal.pone.0058919. Epub 2013 Mar 6. — View Citation

Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF, Gonzalez DG, Peiffert D, van Glabbeke M, Pierart M. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phas — View Citation

Ben-Josef E, Moughan J, Ajani JA, Flam M, Gunderson L, Pollock J, Myerson R, Anne R, Rosenthal SA, Willett C. Impact of overall treatment time on survival and local control in patients with anal cancer: a pooled data analysis of Radiation Therapy Oncology — View Citation

Chakravarthy AB, Catalano PJ, Martenson JA, Mondschein JK, Wagner H, Mansour EG, Talamonti MS, Benson AB. Long-term follow-up of a Phase II trial of high-dose radiation with concurrent 5-fluorouracil and cisplatin in patients with anal cancer (ECOG E4292) — View Citation

Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet. 1996 Oct 19;348(9034) — View Citation

Hosni A, Han K, Le LW, Ringash J, Brierley J, Wong R, Dinniwell R, Brade A, Dawson LA, Cummings BJ, Krzyzanowska MK, Chen EX, Hedley D, Knox J, Easson AM, Lindsay P, Craig T, Kim J. The ongoing challenge of large anal cancers: prospective long term outcom — View Citation

James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS, Saunders MP, Maughan T, McDonald A, Essapen S, Leslie M, Falk S, Wilson C, Gollins S, Begum R, Ledermann J, Kadalayil L, Sebag-Montefiore D. Mitomycin or cisplatin chemoradiation with or withou — View Citation

Lefevre JH, Parc Y, Kerneis S, Shields C, Touboul E, Chaouat M, Tiret E. Abdomino-perineal resection for anal cancer: impact of a vertical rectus abdominis myocutaneus flap on survival, recurrence, morbidity, and wound healing. Ann Surg. 2009 Nov;250(5):7 — View Citation

Morris VK, Salem ME, Nimeiri H, Iqbal S, Singh P, Ciombor K, Polite B, Deming D, Chan E, Wade JL, Xiao L, Bekaii-Saab T, Vence L, Blando J, Mahvash A, Foo WC, Ohaji C, Pasia M, Bland G, Ohinata A, Rogers J, Mehdizadeh A, Banks K, Lanman R, Wolff RA, Strei — View Citation

Moureau-Zabotto L, Viret F, Giovaninni M, Lelong B, Bories E, Delpero JR, Pesenti C, Caillol F, de Chaisemartin C, Minsat M, Monges G, Sarran A, Resbeut M. Is neoadjuvant chemotherapy prior to radio-chemotherapy beneficial in T4 anal carcinoma? J Surg Onc — View Citation

Mullen JT, Rodriguez-Bigas MA, Chang GJ, Barcenas CH, Crane CH, Skibber JM, Feig BW. Results of surgical salvage after failed chemoradiation therapy for epidermoid carcinoma of the anal canal. Ann Surg Oncol. 2007 Feb;14(2):478-83. doi: 10.1245/s10434-006 — View Citation

Nigro ND, Vaitkevicius VK, Considine B Jr. Combined therapy for cancer of the anal canal: a preliminary report. 1974. Dis Colon Rectum. 1993 Jul;36(7):709-11. doi: 10.1007/BF02238600. No abstract available. — View Citation

Nilsson PJ, Svensson C, Goldman S, Ljungqvist O, Glimelius B. Epidermoid anal cancer: a review of a population-based series of 308 consecutive patients treated according to prospective protocols. Int J Radiat Oncol Biol Phys. 2005 Jan 1;61(1):92-102. doi: — View Citation

Northover J, Glynne-Jones R, Sebag-Montefiore D, James R, Meadows H, Wan S, Jitlal M, Ledermann J. Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I). Br J Cancer. 2010 Ma — View Citation

Olsen JR, Moughan J, Myerson R, Abitbol A, Doncals DE, Johnson D, Schefter TE, Chen Y, Fisher B, Michalski J, Narayan S, Chang A, Crane CH, Kachnic L. Predictors of Radiation Therapy-Related Gastrointestinal Toxicity From Anal Cancer Dose-Painted Intensit — View Citation

Ott PA, Piha-Paul SA, Munster P, Pishvaian MJ, van Brummelen EMJ, Cohen RB, Gomez-Roca C, Ejadi S, Stein M, Chan E, Simonelli M, Morosky A, Saraf S, Emancipator K, Koshiji M, Bennouna J. Safety and antitumor activity of the anti-PD-1 antibody pembrolizuma — View Citation

Pan YB, Maeda Y, Wilson A, Glynne-Jones R, Vaizey CJ. Late gastrointestinal toxicity after radiotherapy for anal cancer: a systematic literature review. Acta Oncol. 2018 Nov;57(11):1427-1437. doi: 10.1080/0284186X.2018.1503713. Epub 2018 Sep 28. — View Citation

Rao S, Sclafani F, Eng C, Adams RA, Guren MG, Sebag-Montefiore D, Benson A, Bryant A, Peckitt C, Segelov E, Roy A, Seymour MT, Welch J, Saunders MP, Muirhead R, O'Dwyer P, Bridgewater J, Bhide S, Glynne-Jones R, Arnold D, Cunningham D. International Rare — View Citation

Russo S, Anker CJ, Abdel-Wahab M, Azad N, Bianchi N, Das P, Dragovic J, Goodman KA, Jones W 3rd, Kennedy T, Kumar R, Lee P, Sharma N, Small W, Suh WW, Jabbour SK. Executive Summary of the American Radium Society Appropriate Use Criteria for Treatment of A — View Citation

Sana S, Khan AU. Clinical trials in the management of anal cancer. Clin Colon Rectal Surg. 2009 May;22(2):115-9. doi: 10.1055/s-0029-1223843. — View Citation

Shahjehan F, Kamatham S, Ritter A, Kasi PM. Dramatic response to modified docetaxel, cisplatin, and fluorouracil chemotherapy after immunotherapy in a patient with refractory metastatic anal cancer. Clin Case Rep. 2019 Aug 6;7(9):1729-1734. doi: 10.1002/c — View Citation

Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5. — View Citation

Stewart DB, Gaertner WB, Glasgow SC, Herzig DO, Feingold D, Steele SR; Prepared on Behalf of the Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons. The American Society of Colon and Rectal Surgeons Clinical Practi — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	cCR rate	cCR rate 3 months after treatment	3 months after treatment
Secondary	cCR rate	cCR rate 6 months after treatment	6 months after treatment
Secondary	acute toxicities	acute toxicities	from the start of treatment to 3 months after treatment
Secondary	late toxicities	late toxicities	3 months after treatment
Secondary	colostomy rate	colostomy rate	from the end of treatment to 2 years after treatment
Secondary	local recurrence rate	local recurrence rate	from the end of treatment to 5 years after treatment
Secondary	distant metastasis rate	distant metastasis rate	from the end of treatment to 5 years after treatment
Secondary	progression free survival	progression free survival	from the end of treatment to 5 years after treatment
Secondary	overall sruvival	overall sruvival	from the end of treatment to 5 years after treatment